Pharmacokinetics and Pharmacodynamics of Inhaled GLP-1 (MKC253): Proof-of-Concept Studies in Healthy Normal Volunteers and in Patients With Type 2 Diabetes

Marino, Mark T.; Costello, Diane; Baughman, Ron; Boss, Anders H.; Cassidy, James P.; D'Amico, Cynthia; Marle, Sjoerd van; Vliet, André van; Richardson, Peter

doi:10.1038/clpt.2010.85

Cited by 32 publications

(22 citation statements)

References 33 publications

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“…MannKind is developing an inhalable formulation of native GLP-1 adsorbed to their patented Technosphere microparticles. This drug recently completed a phase Ia clinical trial in which it showed dose-dependent, GLP-1-induced insulin release within six minutes of inhalation in healthy adult males[152]. …”

Section: Glucagon-like Peptide-1 Receptor Agonistsmentioning

confidence: 99%

Controlled release of biologics for the treatment of type 2 diabetes

Gilroy

Luginbuhl

Chilkoti

2016

Journal of Controlled Release

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Type 2 diabetes is a rapidly growing disease that poses a significant burden to the United States healthcare system. Despite the many available treatments for the disease, close to half of diagnosed type 2 diabetes cases are not properly managed, largely due to inadequate patient adherence to prescribed treatment regimens. Methods for improving delivery — and thereby easing administration — of type 2 drugs have the potential to greatly improve patient health. This review focuses on two peptide drugs — insulin and glucagon-like peptide 1 (GLP-1) — for treatment of type diabetes. Peptide drugs offer the benefits of high potency and specificity but pose a significant delivery challenge due to their inherent instability and short half-life. The development of insulin and GLP-1 analogs highlights the broad spectrum of drug delivery strategies that have been used to solve these problems. Numerous structural modifications and formulations have been introduced to optimize absorption, residence time, stability, route of delivery and frequency of administration. Continual improvements in delivery methods for insulin and GLP-1 receptor agonists are paving the way towards better patient compliance and improved disease management, and thereby enhanced patient quality of life.

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Section: Glucagon-like Peptide-1 Receptor Agonistsmentioning

confidence: 99%

Controlled release of biologics for the treatment of type 2 diabetes

Gilroy

Luginbuhl

Chilkoti

2016

Journal of Controlled Release

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“…1 These characteristics enable oral inhalation of therapeutics for a wide range of disease states, 1 providing an alternative delivery route for agents currently dosed only by injection, and by making it possible to bypass hepatic first-pass metabolism by absorption directly into the arterial circulation. 2,3 This technology can accommodate therapeutics over a wide molecular size range 1 and has been used to administer insulin and glucagon-like peptide-1 by the pulmonary route in clinical studies. 3,4 A number of other agents, including oxyntomodulin and peptide YY, have been administered in nonclinical studies.…”

Section: Introductionmentioning

confidence: 99%

“…2,3 This technology can accommodate therapeutics over a wide molecular size range 1 and has been used to administer insulin and glucagon-like peptide-1 by the pulmonary route in clinical studies. 3,4 A number of other agents, including oxyntomodulin and peptide YY, have been administered in nonclinical studies. 5 Therapeutics administered via the Technosphere technology demonstrate rapid absorption, believed to be associated with rapid dissolution of the microparticles rather than any FDKP-mediated absorption enhancement.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic Characterization of the Novel Pulmonary Delivery Excipient Fumaryl Diketopiperazine

Potocka

Cassidy

Haworth

et al. 2010

J Diabetes Sci Technol

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Abbreviations: (ADME) absorption, distribution, metabolism, and excretion, ) area under the curve from time 0 to 480 minutes, (AUC 0-∞ ) area under the curve from time 0 to infinity, (AUC 0-t ) area under the curve from time 0 to t, (BMI) body mass index, (C last ) last observed insulin concentration, (CLD) chronic liver disease, (C max ) maximum observed drug concentration, (DNP) diabetic nephropathy, (FDKP) Bis-3,6(4-fumarylaminobutyl)-2, 5-diketopiperazine, (GFR) glomerular filtration rate, (HPLC) high-performance liquid chromatography, (LSC) liquid scintillation counting, (t 1/2 ) terminal elimination half-life, (t last ) time corresponding to last observed drug concentration, (t max ) time to maximum observed drug concentration Keywords: chronic liver disease, diabetic nephropathy, fumaryl diketopiperazine, inhalation, Technosphere

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“…A MM da amilopectina pode atingir milhões de Dalton. O uso de microesferas baseadas em amido foi sugerido para embolização [51] , administração parenteral e administração nasal [52] de diferentes princípios ativos.…”

Section: Amidounclassified

Polímeros usados como sistemas de transporte de princípios ativos

Severino¹,

Santana

Malmonge

et al. 2011

Polímeros

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Resumo: Os diferentes sistemas de transporte têm evidenciado potencial terapêutico para uma grande variedade de princípios ativos, satisfazendo vários requisitos, como a prevenção da sua eliminação rápida do organismo, a redução da sua toxicidade sistêmica, a estabilização e a otimização do seu metabolismo, e o direcionamento específico ao local alvo e os mecanismos de defesa. No entanto, têm sido reconhecidos vários outros desafios associados à liberação específica do princípio ativo ao local alvo, pelo que, para ultrapassar os obstáculos químicos e biológicos, a seleção do polímero utilizado para a preparação do sistema de transporte é de importância crucial. O presente trabalho apresenta um relato sobre os principais polímeros naturais e sintéticos utilizados para a preparação de sistemas de transporte de princípios ativos in vivo. Palavras-chaves: Polímeros sintéticos, polímeros naturais, transporte de princípios ativos. Polymers for Drug Delivery Systems FormulationsAbstract: The different carrier systems have shown therapeutic potential for a wide variety of drugs, satisfying multiple requirements, such as prevention of rapid elimination, reducing toxicity, promoting stabilization, optimization of metabolism, drug delivery and defense mechanisms. However, it has been recognized several other challenges associated with the specific release of actives in drug delivery. Therefore, to overcome chemical and biological obstacles, the selection of the polymer used to prepare the transport system is crucial. This paper presents a report on the main natural and synthetic polymers used in the preparation of drug carrier systems in vivo. Keywords: Synthetic polymers, natural polymers, carrier of drugs. IntroduçãoA investigação científica de novos meios de veiculação de princípios ativos in vivo permitiu o desenvolvimento de vários tipos de sistemas de transporte dos quais se destacam os lipossomas [1] , conjugados de polímero e princípios ativos [2] , micelas de copolímeros anfipáticos [3] , micro e nanopartículas poliméricas [4] e, mais recentemente, as nanopartículas lipídicas sólidas [5] . Os diferentes sistemas de transporte têm evidenciado potencial terapêutico para uma grande variedade de princípios ativos, preenchendo assim vários requisitos, como a prevenção da sua eliminação rápida do organismo [6] , a redução da sua toxicidade sistêmica [7] , a estabilização e a otimização do seu metabolismo [8] , o direcionamento específico ao local alvo [9] e os mecanismos de defesa [10] . No entanto, têm sido reconhecidos vários outros desafios associados à liberação específica do princípio ativo ao local alvo, pelo que, para ultrapassar os obstáculos químicos e biológicos, a seleção do polímero utilizado para a preparação do sistema de transporte é de importância crucial.Para a preparação dos sistemas poliméricos de transporte, pode recorrer-se ao uso de polímeros naturais [11] , sintéticos [12] ou semi-sintéticos [13] . A seleção do polímero a ser empregado está condicionada, em grande medida pela natureza do princípio...

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Pharmacokinetics and Pharmacodynamics of Inhaled GLP-1 (MKC253): Proof-of-Concept Studies in Healthy Normal Volunteers and in Patients With Type 2 Diabetes

Cited by 32 publications

References 33 publications

Controlled release of biologics for the treatment of type 2 diabetes

Controlled release of biologics for the treatment of type 2 diabetes

Pharmacokinetic Characterization of the Novel Pulmonary Delivery Excipient Fumaryl Diketopiperazine

Polímeros usados como sistemas de transporte de princípios ativos

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